1. Field of the Invention
The present invention relates to a pharmaceutical composition, and more particularly to a composition comprising mesenchymal stem cells, a hyaluronan and a pharmaceutically acceptable carrier.
2. Description of Related Art
Osteoarthritis (hereinafter also referred to as OA) is a worldwide health problem among the elderly, affecting over 70% of Americans between the ages of 55 and 70 years old. It is caused by progressive chondral damage due to chronic trauma or diseases. Articular cartilage has a limited capacity for repair because of the avascularity and low cellular mitotic activity.
The cause of osteoarthritis formulation involves several pathological mechanisms, including enzymatic degradation of the extracellular matrix (hereinafter also referred to as ECM), deficient new matrix formation, cell death, and abnormal activation and hypertrophic differentiation of cartilage cells. Many treatment methods have been developed to decrease pain and improve the affected functions in individuals. However, current strategies such as total joint arthroplasty are unable to restore the native structure of cartilage and may even increase further risk of articulation damage.
Recent researches have developed a treatment for osteoarthritis by bone and cartilage generated from the bone marrow mesenchymal stem cells (hereinafter also referred to as BMSCs). While this technique is appealing, the harvest of bone marrow is painful and yields a limited number of stem cells, especially in the elderly. Thus, an extensive expansion of the stem cells in culture is desired. Adipose-derived mesenchymal stem cells (hereinafter also referred to as ASCs) are currently the best choice since they can be obtained in larger amounts with less morbidity and can be easily expanded in vitro. In addition to regeneration activity, ASCs also exhibit immunosuppressive properties. Recently, cells with stem cell characteristics have been reported in the infra-patellar fat pad (hereinafter also referred to as IFP).
The ECM provides a micro-environment for cells to maintain homeostasis and differentiate to the specific tissues. In the ECM, hyaluronan (hereinafter also referred to as HA) is the main glycosaminoglycan in the mesenchyme of early chondrogenesis and is native in the cartilage tissue. As the major physiological component of the articular cartilage matrix, HA is particularly abundant in synovial fluid. This polymer plays a role in cartilage homeostasis and is involved in cellular processes such as cell morphogenesis, proliferation, and wound repair. It is also widely used for the intra-articular treatment of OA. However, the effect of HA micro-environment on mesenchymal stem cells (hereinafter also referred to as MSCs) differentiation has rarely been reported.